Emerging evidence for a mechanistic link between low-frequency oscillation of ventricular repolarization measured from the electrocardiogram T-wave vector and arrhythmia.

Strong recent clinical evidence links the presence of prominent oscillations of ventricular repolarization in the low-frequency range (0.04-0.15 Hz) to the incidence of ventricular arrhythmia and sudden death in post-MI patients and patients with ischaemic and non-ischaemic cardiomyopathy. It has been proposed that these oscillations reflect oscillations of ventricular action potential duration at the sympathetic nerve frequency. Here we review emerging evidence to support that contention and provide insight into possible underlying mechanisms for this association.

Left atrial scarring and conduction velocity dynamics: Rate dependent conduction slowing predicts sites of localized reentrant atrial tachycardias.

BACKGROUND: Low voltage zones (LVZs) are associated with conduction velocity (CV) slowing. Rate-dependent CV slowing may play a role in reentry mechanisms. METHODS: Patients undergoing catheter ablation for AT were enrolled. Aim was to assess the relationship between rate-dependent CV slowing and sites of localized reentrant atrial tachycardias (AT). On a bipolar voltage map regions were defined as non-LVZs [≥0.5 mV], LVZs [0.2-0.5 mV] and very-LVZs [<0.2 mV]. Unipolar electrograms were recorded with a 64-pole basket catheter during uninterrupted atrial pacing at four pacing intervals (PIs) during sinus rhythm. CVs were measured between pole pairs along the wavefront path. Sites of rate-dependent CV slowing were defined as exhibiting a reduction in CV between PI = 600 ms and 250 ms of ≥20% more than the mean CV reduction seen between these PIs for that voltage zone. Rate-dependent CV slowing sites were correlated to sites of localized reentrant ATs as confirmed with conventional mapping, entrainment and response to ablation. RESULTS: Eighteen patients were included (63 ±â€¯10 years). Mean CV at 600 ms was 1.53 ±â€¯0.19 m/s in non-LVZs, 1.14 ±â€¯0.15 m/s in LVZs, and 0.73 ±â€¯0.13 m/s in very-LVZs respectively (p < 0.001). Rate-dependent CV slowing sites were predominantly in LVZs [0.2-0.5 mV] (74.4 ±â€¯10.3%; p < 0.001). Localized reentrant ATs were mapped to these sites in 81.8% of cases (sensitivity 81.8%, 95% CI 48.2-97.9% and specificity 83.9%, 95% CI 81.8-86.0%). Macro-reentrant or focal ATs were not mapped to sites of rate-dependent CV slowing. CONCLUSIONS: Rate-dependent CV slowing sites are predominantly confined to LVZs [0.2-0.5 mV] and the resultant CV heterogeneity may promote reentry mechanisms. These may represent a novel adjunctive target for AT ablation.

Assessment of a conduction-repolarisation metric to predict Arrhythmogenesis in right ventricular disorders.

BACKGROUND: The re-entry vulnerability index (RVI) is a recently proposed activation-repolarization metric designed to quantify tissue susceptibility to re-entry. This study aimed to test feasibility of an RVI-based algorithm to predict the earliest endocardial activation site of ventricular tachycardia (VT) during electrophysiological studies and occurrence of haemodynamically significant ventricular arrhythmias in follow-up. METHODS: Patients with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) (n = 11), Brugada Syndrome (BrS) (n = 13) and focal RV outflow tract VT (n = 9) underwent programmed stimulation with unipolar electrograms recorded from a non-contact array in the RV. RESULTS: Lowest values of RVI co-localised with VT earliest activation site in ARVC/BrS but not in focal VT. The distance between region of lowest RVI and site of VT earliest site (Dmin) was lower in ARVC/BrS than in focal VT (6.8 ±â€¯6.7 mm vs 26.9 ±â€¯13.3 mm, p = 0.005). ARVC/BrS patients with inducible VT had lower Global-RVI (RVIG) than those who were non-inducible (-54.9 ±â€¯13.0 ms vs -35.9 ±â€¯8.6 ms, p = 0.005) or those with focal VT (-30.6 ±â€¯11.5 ms, p = 0.001). Patients were followed up for 112 ±â€¯19 months. Those with clinical VT events had lower Global-RVI than both ARVC and BrS patients without VT (-54.5 ±â€¯13.5 ms vs -36.2 ±â€¯8.8 ms, p = 0.007) and focal VT patients (-30.6 ±â€¯11.5 ms, p = 0.002). CONCLUSIONS: RVI reliably identifies the earliest RV endocardial activation site of VT in BrS and ARVC but not focal ventricular arrhythmias and predicts the incidence of haemodynamically significant arrhythmias. Therefore, RVI may be of value in predicting VT exit sites and hence targeting of re-entrant arrhythmias.

Mechano-electrical feedback in the clinical setting: Current perspectives.

Mechano-electric feedback (MEF) is an established mechanism whereby myocardial deformation causes changes in cardiac electrophysiological parameters. Extensive animal, laboratory and theoretical investigation has demonstrated that abnormal patterns of cardiac strain can induce alteration of electrical excitation and recovery through MEF, which can potentially contribute to the establishment of dangerous arrhythmias. However, the clinical relevance of MEF in patients with heart disease remains to be established. This paper reviews up-to date experimental evidence describing the response to different types of mechanical stimuli in the intact human heart with the support of new data collected during cardiac surgery. It discusses modulatory effects of MEF that may contribute to increase the vulnerability to arrhythmia and describes MEF interaction with clinical conditions where mechanically induced changes in cardiac electrophysiology are likely to be more relevant. Finally, directions for future studies, including the need for in-vivo human data providing simultaneous assessment of the distribution of structural, functional and electrophysiological parameters at the regional level, are identified.

Respiratory rate estimation from multilead directions, based on ECG delineation.

Estimating the instantaneous respiratory rate (Rr) from the electrocardiogram (ECG) is of interest as respiration direct measurement in clinical situations is often cumbersome. In this study, the Rr was estimated from the same Final Directions of maximum projection (FD) used for multi lead ECG automatic delineation. Power spectral analysis over the directions based on QRS complex main peak and T wave onset, peak and end spatial loops was used for Rr estimation. On a subset of the Physionet MGH/MF dataset, the proposed method yielded more accurate Rr estimates (minimum mean absolute error (MAE), 2.82 bpm) than the frequency tracking algorithm (minimum MAE, 4.53 bpm) and Fourier-based frequency estimation (minimum MAE, 4.94 bpm) using each lead alone, outperforming also the weighted multi-signal oscillator-based algorithm estimates for two or three lead (minimum MAE, 3.04 bpm). It was also shown that the FD of the three orthogonalized leads from Principal Component algorithm, improve the performance of Rr estimation.

Assessing real-time RR-QT frequency-domain measures of coupling and causality through inhomogeneous point-process bivariate models.

Ventricular repolarization instability is known to be related to arrhythmogenesis and increased risk of sudden cardiac death. These repolarization dynamics are linked to the distance between T-wave and Q-wave occurrences (QT) on the ECG, and they are coupled with R-wave to R-wave interval variability (RRV). Several efforts have been dedicated to the analysis of QT-RR interactions in order to provide both a quantification of the coupling and estimates of intrinsic repolarization dynamics. However, a methodology able to quantify dynamic changes in repolarization variability unrelated to RRV dynamics is still needed. In this study, we propose a bivariate model embedded within a multiple inhomogeneous point-process framework to obtain time-varying tracking of (causal) interactions between QT variability (QTV), a marker of repolarization variability, and RRV. Data from 15 healthy subjects undergoing a tilt table test were analyzed. Our results demonstrate that the model effectively captures the time-varying mutual QTV-RRV interactions. The analysis of time-varying coherence confirms that head-up tilt is associated with a decrease in linear QTV-RRV coupling, while time-varying directed coherence shows that intrinsic QTV becomes more prominent during head-up tilt.

Cross time-frequency analysis for combining information of several sources: application to estimation of spontaneous respiratory rate from photoplethysmography.

A methodology that combines information from several nonstationary biological signals is presented. This methodology is based on time-frequency coherence, that quantifies the similarity of two signals in the time-frequency domain. A cross time-frequency analysis method, based on quadratic time-frequency distribution, has been used for combining information of several nonstationary biomedical signals. In order to evaluate this methodology, the respiratory rate from the photoplethysmographic (PPG) signal is estimated. The respiration provokes simultaneous changes in the pulse interval, amplitude, and width of the PPG signal. This suggests that the combination of information from these sources will improve the accuracy of the estimation of the respiratory rate. Another target of this paper is to implement an algorithm which provides a robust estimation. Therefore, respiratory rate was estimated only in those intervals where the features extracted from the PPG signals are linearly coupled. In 38 spontaneous breathing subjects, among which 7 were characterized by a respiratory rate lower than 0.15 Hz, this methodology provided accurate estimates, with the median error {0.00; 0.98} mHz ({0.00; 0.31}%) and the interquartile range error {4.88; 6.59} mHz ({1.60; 1.92}%). The estimation error of the presented methodology was largely lower than the estimation error obtained without combining different PPG features related to respiration.

Assessment of the dynamic interactions between heart rate and arterial pressure by the cross time-frequency analysis.

In this study, a framework for the characterization of the dynamic interactions between RR variability (RRV) and systolic arterial pressure variability (SAPV) is proposed. The methodology accounts for the intrinsic non-stationarity of the cardiovascular system and includes the assessment of both the strength and the prevalent direction of local coupling. The smoothed pseudo-Wigner-Ville distribution (SPWVD) is used to estimate the time-frequency (TF) power, coherence, and phase-difference spectra with fine TF resolution. The interactions between the signals are quantified by time-varying indices, including the local coupling, phase differences, time delay, and baroreflex sensitivity (BRS). Every index is extracted from a specific TF region, localized by combining information from the different spectra. In 14 healthy subjects, a head-up tilt provoked an abrupt decrease in the cardiovascular coupling; a rapid change in the phase difference (from 0.37 ± 0.23 to -0.27 ± 0.22 rad) and time delay (from 0.26 ± 0.14 to -0.16 ± 0.16 s) in the high-frequency band; and a decrease in the BRS (from 23.72 ± 7.66 to 6.92 ± 2.51 ms mmHg(-1)). In the low-frequency range, during a head-up tilt, restoration of the baseline level of cardiovascular coupling took about 2 min and SAPV preceded RRV by about 0.85 s during the whole test. The analysis of the Eurobavar data set, which includes subjects with intact as well as impaired baroreflex, showed that the presented methodology represents an improved TF generalization of traditional time-invariant methodologies and can reveal dysfunctions in subjects with baroreflex impairment. Additionally, the results also suggest the use of non-stationary signal-processing techniques to analyze signals recorded under conditions that are usually supposed to be stationary.

Photoplethysmography pulse rate variability as a surrogate measurement of heart rate variability during non-stationary conditions.

In this paper we assessed the possibility of using the pulse rate variability (PRV) extracted from the photoplethysmography signal as an alternative measurement of the HRV signal in non-stationary conditions. The study is based on analysis of the changes observed during a tilt table test in the heart rate modulation of 17 young subjects. First, the classical indices of HRV analysis were compared to the indices from PRV in intervals where stationarity was assumed. Second, the time-varying spectral properties of both signals were compared by time-frequency (TF) and TF coherence analysis. Third, the effect of replacing PRV with HRV in the assessment of the changes of the autonomic modulation of the heart rate was considered. Time-invariant HRV and PRV indices showed no statistically significant differences (p > 0.05) and high correlation (>0.97). Time-frequency analysis revealed that the TF spectra of both signals were highly correlated (0.99 +/- 0.01); the difference between the instantaneous power, in the LF and HF bands, obtained from HRV and PRV was small (<10(-3) s(-2)) and their temporal patterns were highly correlated (0.98 +/- 0.04 and 0.95 +/- 0.06 in the LF and HF bands, respectively) and TF coherence in the LF and HF bands was high (0.97 +/- 0.04 and 0.89 +/- 0.08, respectively). Finally, the instantaneous power in the LF band was observed to significantly increase during head-up tilt by both HRV and PRV analysis. These results suggest that although some differences in the time-varying spectral indices extracted from HRV and PRV exist, mainly in the HF band associated with respiration, PRV could be used as a surrogate of HRV during non-stationary conditions, at least during the tilt table test.